Evaluation of dimethylaminosulfonates of alkane diols as a novel group of anticancer agents

A series of title compounds has been synthesized and evaluated by the cytot oxicity assays conducted in vitro in seven human tumor cell lines, initiall y in MT-4 and H-9, followed by U-937, PM-I, MCF-7, Hep-3B, and K-562. These compounds were simultaneously compared with the existing clinical drug, bu sulfan and also with an experimental drug, hepsulfam. IC50 values of these agents in T-cell lymphoma and leukemic cell lines indicate that two of thes e agents hexsulfamyl and octsulfamyl (compounds 3 and 4) were significantly more potent than busulfan and were comparable in antileukemic activity wit h hepsulfam. In order to determine the effect of these agents on normal pro liferating cells, the toxicity of 3 and 4 was also determined in vitro agai nst human peripheral blood mononuclear cells (PBMC) and against murine bone marrow progenitor cells. PBMC assay data indicate that these agents were g enerally less toxic than hepsulfam. The results of the colony forming unit- erythroid (CFU-E) and granulocyte-macrophage colony forming unit (CFU-GM) a ssays, however, indicate that these agents were more toxic than hepsulfam t o erythroid progenitor cells than to granulocyte-macrophage progenitors. Th e toxicity of octsulfamyl was further assessed in vivo in normal Swiss mice by measuring drug-induced changes in hematological parameters, femoral bon e marrow cellularity and splenic cellularity as well as hepatotoxicity and nephrotoxicity on day 7 and 14 following drug treatment at the dose of 1.0 mg/kg body weight from days 1 to 5. The results indicate that the compound did not adversely affect hematopoiesis. Marginal bone marrow suppression wa s observed on day 7, which gradually tends to reach normalcy on day 14. The other parameters were within normal limit. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.